Defining Stromal-Cancer Cell Interactions For Xenografting Human Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$559,635.00
Summary
Prostate Cancer research continues to be hindered by a lack of laboratory models to understand disease progression and design new drugs to cure the disease. In this study, we propose to use a new and reliable method of growing human prostate cancer tissue in mice. Using this model, we will investigate the role of hormone signalling and cellular communication in prostate cancer that may lead to new therapies for men diagnosed with organ-confined disease.
Each year, 18,000 Australian men are diagnosed with prostate cancer. While current treatments are designed to directly target cancer cells, the tumour-associated stroma is also recognised to play a pivotal in the establishment and progression of prostate cancer. This grant aims to investigate the contribution of stromal Hedgehog signalling, with the view to creating new treatment strategies that will treat the entire tumor environment.
Using Bioengineered 3D Models To Replicate The Tumour Microenvironment In Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$339,658.00
Summary
The research will address the poor prognosis of patients with advanced prostate cancer bone metastasis by establishing a novel 3D bioengineered bone model containing high amounts of fat cells, where cancer cells can relocate. This approach will help identifying the impact of fat cells on cancer cell function, and help determine whether fat cells are legitimate therapeutic targets, ultimately assisting clinicians to select better therapies for prostate cancer bone metastasis.
Metagenomic Analysis To Determine The Prostate Microenvironment And The Aetiology Of Inflammatory Mediated Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$339,534.00
Summary
Infectious organisms have been implicated in the development of several different malignancies. This project aims to determine if this may also be applicable in prostate cancer and if so, to define which organism/s may be responsible, thus providing targets for improving diagnosis, treatment and prevention strategies. The approach will be to identify DNA in the prostate tumour tissue that is foreign to the �normal� prostate environment and indicative of an invading organism.
The Ghrelin Axis As A Target For Prostate Cancer Therapy
Funder
National Health and Medical Research Council
Funding Amount
$585,497.00
Summary
Prostate cancer affects one in nine Australian men in their lifetime, and although there have been great advances in treatments, advanced prostate cancer remains incurable. Current treatments often lead to side effects which affect quality of life. We have found that the appetite hormone, ghrelin, stimulates prostate cancer cell growth and may be a useful target for prostate cancer therapy. We predict that targeting the ghrelin axis will prevent some of the side effects of other treatments that ....Prostate cancer affects one in nine Australian men in their lifetime, and although there have been great advances in treatments, advanced prostate cancer remains incurable. Current treatments often lead to side effects which affect quality of life. We have found that the appetite hormone, ghrelin, stimulates prostate cancer cell growth and may be a useful target for prostate cancer therapy. We predict that targeting the ghrelin axis will prevent some of the side effects of other treatments that reduce quality of life for patients.Read moreRead less
Estrogen Therapy For Castrate Resistant Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$531,690.00
Summary
Withdrawal of male hormones in men with prostate cancer is effective therapeutically because it causes cell death in most of the tumour. However the remaining cells (called castrate resistant cells), give rise to recurrent disease that inevitably kills the patient. This project aims to test if our compound will kill these cells and prevent recurrence or if it has any benefit for the patients who have incurable disease.
Some advances have been made in identifying genetic factors that underlie susceptibility to prostate cancer but few explain multiple-cases of prostate cancer in families. Linkage studies show that the unexplained familial aggregations of prostate cancer are likely to be explained by mutations in many genes. This research will utilize our prior research, our extensive research resources, new technology and supercomputing to identify genetic factors associated with prostate cancer susceptibility.
Investigation Of Steroidogenesis As A Mechanism Of Castration Resistance In Human Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$419,076.00
Summary
Prostate cancer is critically dependent upon continued testosterone stimulation, even when the disease becomes resistant to existing hormonal therapies that suppress serum levels. The source of this testosterone is currently unclear. This study aims to identify the site of testosterone synthesis in patients with prostate cancer, and determine the relevance of continued testosterone signalling in patients treated with 'super castrating' hormonal therapy.
A Novel Strategy For Targeting Castrate-resistant Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$799,440.00
Summary
Modern drugs for advanced prostate cancer are based on starving the tumour of hormones. However, tumours either escape this treatment or are inherently resistant to it. We have developed a new approach with drugs that block protein synthesis. This deprives tumours of the building blocks to make new cancer cells. In this project, we will determine the effectiveness of this new treatment on samples of patient prostate cancer tissue that have failed currently available drugs.
Prognostic Importance Of Androgen Receptors In Epithelium And Stroma In Early Stage Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$348,750.00
Summary
The use of serum prostate specific antigen (PSA) to screen asymptomatic men for prostate cancer has reduced the stage of disease at diagnosis. The majority of tumours are now small and potentially organ-confined. The use of nomograms, algorithms based on preoperative clinical features of these patients (serum PSA level, Gleason grade, clinical stage) has facilitated this process, but is imperfect as 20-30% of patients experience disease relapse within 5-7 years. Tumours with similar preoperative ....The use of serum prostate specific antigen (PSA) to screen asymptomatic men for prostate cancer has reduced the stage of disease at diagnosis. The majority of tumours are now small and potentially organ-confined. The use of nomograms, algorithms based on preoperative clinical features of these patients (serum PSA level, Gleason grade, clinical stage) has facilitated this process, but is imperfect as 20-30% of patients experience disease relapse within 5-7 years. Tumours with similar preoperative clinical features have markedly different outcomes, reinforcing the inadequacy of current approaches to determining whether or not an individual patient has organ-confined disease. A new approach is to incorporate into the standard diagnostic nomograms, biological features from preoperative core biopsy linked to the process of disease relapse, and which independently predict patient outcome risk group. Our preliminary studies using a small hypothesis-generating cohort of patients with early stage prostate cancer determined that elevated levels of androgen receptors (AR) in malignant epithelial cells and reduced levels of AR in peritumoral stromal cells independently predict disease relapse after surgery. In this project, AR measurements will be analysed in independent cohorts of patients derived from two Australian institutions to determine whether the predictive value is maintained across multi-Institutional cohorts. Selected androgen-regulated markers of tumour growth and spread (proliferative, apoptotic, metastatic) will be examined in microarrayed postoperative tissue samples. The postoperative markers will be examined for independence of prediction of relapse. Independent markers will be examined for ability to increase predictive efficacy in standard diagnostic nomograms. Levels of the two markers with greatest predictive value will be measured in preoperative core biopsies and tested for predictive ability as a prelude to clinical practice.Read moreRead less